This work involves the study of various problems in transplantation therapy for leukemia using a mouse model with a viral induced lymphoid leukemia. The model, as developed in our laboratories, employs a number of mouse strains of varying resistance of sensitivity to the leukemogenic virus which are employed as donor animals, and a particular leukemia sensitive strain (SJL/J) which is employed as the transplantation recipient. In addition to the allogeneic strains we have also developed a leukemia virus resistant hybrid to the SJL/J which is histocompatible to that strain and utilized in certain of the studies. In the forthcoming year the research on this grant will be concerned with the study of major and minor histocompatibility factors and their role in the development of graft-vs-host disease, and their effect in determining anti-leukemic properties of the graft. We have also recently described the kinetics of fatal acute graft-vs-host disease following the transplantation of allogeneic spleen cells and have obtained evidence that the effector cells for the fatal response may be cells already partially differentiated and in the host marrow or spleen at the time of transplant. Our evidence also suggests that these cells may have a limited functional life-time, and if they can be eliminated or suppressed the probability of fatal GvH development can be lessened. In the coming period our studies will be also concerned with trying to characterize these cells and determining if they differ from immunocompetent cells responsible for anti-leukemic activity in the marrow graft.